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Active ingredients
Metoprolol
Release form
Pills
Composition
Metoprolol tartrate 100 mg adjuvants: lactose monohydrate, magnesium stearate, microcrystalline cellulose, sodium carboxymethyl starch, anhydrous silicon dioxide colloid, povidone.
Pharmacological effect
Metoprolol is a β1-adrenergic blocker that blocks β1 receptors at doses significantly lower than the doses required to block β2 receptors. Metoprolol has an insignificant membrane stabilizing effect and does not exhibit partial agonist activity. Metoprolol reduces or inhibits the agonistic effect that catecholamines have on cardiac activity, which are released during nervous and physical stress. This means that metoprolol has the ability to prevent an increase in heart rate, minute volume and increased cardiac contractility, as well as an increase in blood pressure caused by an abrupt release of catecholamines. Metoprolol can be prescribed for patients with symptoms of obstructive pulmonary disease in combination with β2 adrenomimetic drugs. When used together with β2-adrenergic agonists, Betaloc in therapeutic doses has less effect on bronchodilation caused by β2-adrenomimetics than non-selective β-adrenergic blockers. Metoprolol to a lesser extent than non-selective β-blockers affects insulin production and carbohydrate metabolism. The effect of Betaloc on the reaction of the cardiovascular system in hypoglycemia is much less pronounced compared to non-selective β-adrenergic blockers. Clinical studies have shown that Betaloc may cause a slight increase in triglyceride levels and a decrease in the content of free fatty acids in the blood. In some cases, there was a slight decrease in the fraction of high-density lipoprotein (HDL), which is less pronounced than in the case of non-selective P-blockers. However, in one of the clinical studies it was shown a significant decrease in the level of total cholesterol in the blood serum during the treatment with metoprolol for several years. The quality of life during the period of treatment with the drug Betaloc does not worsen or improves. Improving the quality of life during treatment with the drug Betaloc was observed in patients after myocardial infarction.
Pharmacokinetics
Metoprolol is almost completely absorbed after ingestion. When taking the drug within the range of therapeutic doses, the concentration of the drug in the blood plasma is linearly dependent on the dose taken. TCmax 1.5-2 hours after taking the drug. After ingestion of the first dose of metoprolol systemic circulation reaches about 50% of the dose. With repeated receptions, the indicator of systemic bioavailability increases to 70%. Taking the drug with food can increase systemic bioavailability by 30-40%. Communication with plasma proteins is low, about 5-10%. Metabolism and excretionMethoprolol undergoes oxidative metabolism in the liver with the formation of 3 major metabolites, none of which have a clinically significant β-blocking effect. About 5% of the dose taken are eliminated with urine in unchanged form, in some cases, this figure can reach 30%. The average T1 / 2 of metoprolol from plasma is about 3.5 hours (minimum - 1 hour, maximum - 9 hours). Plasma clearance is approximately 1 l / min. In elderly patients, there are no significant changes in the pharmacokinetics of metoprolol compared with young patients. Systemic bioavailability and excretion of metoprolol does not change in patients with reduced kidney function. The removal of metabolites in these patients, however, is reduced. Significant accumulation of metabolites was observed in patients with glomerular filtration rate of less than 5 ml / min. However, this accumulation of metabolites does not enhance the P-blocking effect. In patients with reduced liver function, the pharmacokinetics of metoprolol (due to the low level of association with proteins) varies slightly. However, in patients with severe cirrhosis or portocaval anastomosis, the bioavailability of metoprolol may increase, and the total clearance may decrease. In patients with portocaval anastomosis, the total clearance was approximately 300 ml / min, and the area under the plasma concentration curve — time (AUC) was 6 times greater than in healthy patients.
Indications
- arterial hypertension: reduction of arterial pressure and reduction of the risk of cardiovascular and coronary death (including sudden death); - angina pectoris; - cardiac rhythm disturbances, including supraventricular tachycardia; - prevention of migraine attacks; - hyperthyroidism (complex therapy).
Contraindications
- atrioventricular block II and III; heart failure in the stage of decompensation; - patients receiving long-term or intermittent inotropic therapy and acting on beta-adrenergic receptors; - clinically significant sinus bradycardia; - sick sinus syndrome; - cardiogenic shock; peripheral circulation disorders - arterial hypotension - Betaloc is contraindicated in patients with acute myocardial infarction with a heart rate less than 45 beats per minute, PQ interval more than 0.24 seconds or systolic a with a pressure of less than 100 mm Hg - in severe peripheral vascular diseases with a threat of gangrene - in patients receiving β-blockers, intravenous administration of blockers of “slow” calcium channels like verapamil is contraindicated - age up to 18 years (efficacy and safety have not been established ); - known hypersensitivity to metoprolol and its components or to other β-adrenergic blockers. With care: atrioventricular block I degree, Prinzmetal angina, chronic obstructive disease l lung (emphysema, chronic obstructive bronchitis, bronchial asthma), diabetes mellitus, severe renal failure.
Precautionary measures
During treatment, psoriasis may worsen. During pheochromocytoma, propranolol can only be used after taking an alpha blocker. After a long course of treatment, propranolol should be discontinued gradually, under the supervision of a physician. during anesthesia, you must stop taking propranolol or find a remedy for anesthesia with minimal negative inotropic effects. The impact on the ability to drive vehicles and control mechanisms of patients whose activities require increased attention, the question of the use of propranolol on an outpatient basis should be addressed only after evaluating the individual response of the patient.
Use during pregnancy and lactation
Like most drugs, Betaloc should not be prescribed during pregnancy and during breastfeeding, unless the expected benefit to the mother outweighs the potential risk to the fetus and / or the baby.Like other antihypertensive drugs, β-blockers can cause side effects, such as bradycardia in the fetus, newborns or babies who are breastfed. The amount of metoprolol released into breast milk and the β-blocking effect on a baby who is breastfed ( when metoprolol is taken by the mother at therapeutic doses, they are insignificant.
Dosage and administration
Tablets can be taken both with food and on an empty stomach. Arterial hypertension 100-200 mg of the drug Betaloc once in the morning or in two doses; in the morning and in the evening. If necessary, the dose can be increased or another antihypertensive agent can be added. Long-term antihypertensive therapy 100-200 mg of Betaloc per day can reduce overall mortality, including sudden death, as well as the incidence of cerebral stroke and impaired coronary blood circulation in patients with hypertension. mg per day in two doses; in the morning and in the evening. If necessary, another antianginal medication may be added to the therapy. Violations of the heart rhythm 100-200 mg per day in two doses; in the morning and in the evening. If necessary, another antiarrhythmic drug may be added to the therapy. Supportive therapy after myocardial infarction. The maintenance dose is 200 mg per day in two doses; in the morning and in the evening. Appointment of Betaloc at a dose of 200 mg per day reduces mortality in patients after myocardial infarction and reduces the risk of recurrent myocardial infarction (including in patients with diabetes). Functional disturbances of cardiac activity, accompanied by tachycardia 100 mg of Betacal once day, it is recommended to take a pill in the morning. If necessary, the dose can be increased. Prevention of migraine attacks 100-200 mg per day in two doses; morning and evening. Hyperthyroidism 150–200 mg per day in 3–4 doses. Kidney dysfunction. There is no need to adjust the dose in patients with impaired renal function. Liver dysfunction. Usually, metoprolol dose adjustment is not required due to low plasma protein binding. However, in severe liver dysfunction (in patients with severe liver cirrhosis or portocaval anastomosis), a dose reduction may be required. Older age There is no need to adjust the dose in elderly patients. The experience with the drug Betaloc in children is limited.
Side effects
Betaloc is well tolerated by patients, the side effects are mainly mild and reversible. As a result of clinical studies or when using the drug Betaloc (metoprolol tartrate), the following undesirable side effects have been described in clinical practice. In many cases, a causal relationship with taking the drug Betaloc has not been established. The following criteria were used to assess the frequency of cases: very often (> 10%), often (1-9.9%), infrequently (0.1-0.9%), rarely (0.01-0.09%) and very rarely (<0.01%). vascular system Frequently: bradycardia, postural disorders (very rarely accompanied by fainting), cold extremities, palpitations. Infrequently: temporary strengthening of symptoms of heart failure, AV blockade of the I degree; cardiogenic shock in patients with acute myocardial infarction. Seldom: other disturbances of cordial conductivity, arrhythmias. Very rarely: gangrene in patients with previous severe disorders of the peripheral circulation. CNS. Very often: increased fatigue. Often: dizziness, headache. Rarely: increased nervous irritability, anxiety, impotence / sexual dysfunction. Infrequently: paresthesias, convulsions, depression, weakening of attention, drowsiness or insomnia, nightmares. Very rarely: amnesia / memory impairment, depression, hallucinations. GIT Frequently: nausea, abdominal pain, diarrhea, constipation. Infrequently: vomiting. Rarely: dry mouth. LiverRedko: abnormal liver function. Very rarely: hepatitis. Skin covers. Infrequently: rash (in the form of urticaria), excessive sweating. Rarely: hair loss. Very rarely: photosensitization, exacerbation of psoriasis. Respiratory disorders. Frequently: dyspnea on physical exertion. Infrequently: bronchospasm. Rarely: rhinitis. Sensory organs. Rare: visual impairment, dryness and / or eye irritation, conjunctivitis. Very rarely: tinnitus, taste disturbances. From the musculoskeletal system: Very rarely: arthralgia. Substance: Infrequently: weight gain. Blood. Very rare: thrombocytopenia.
Overdose
Symptoms The consequences of an overdose of Betaloc can be a pronounced decrease in blood pressure, sinus bradycardia, atrioventricular blockade, heart failure, cardiogenic shock, cardiac arrest, bronchospasm, impaired consciousness / coma, nausea, vomiting and cyanosis. lead to deterioration of the patient.The first signs of overdose may occur within 20 minutes - 2 hours after taking the drug. Treatment Accept activated carbon, if necessary, gastric lavage. In the case of a pronounced decrease in blood pressure, bradycardia, or the threat of heart failure, β1-adrenomimetic (for example, dobutamine) should be administered intravenously at intervals of 2–5 minutes or infusion until therapeutic effect is achieved. If the selective Pi agonist is unavailable, intravenous dopamine or atropine sulfate can be administered to block the vagus nerve. If the therapeutic effect is not achieved, other sympathomimetics can be used, such as dobutamine or norepinephrine. Glucagon can be administered in a dose of 1-10 mg. Sometimes it may be necessary to use a heart rate driver. For the relief of bronchospasm, β2-adrenomimetic should be administered intravenously. It is necessary to take into account that the doses of antidotes necessary to alleviate the symptoms resulting from an overdose of β-adrenergic blockers are much higher than therapeutic, since β-adrenoreceptors are in a bound state with a β-adrenergic blocker.
Interaction with other drugs
Joint administration of the drug Betaloc with the following drugs should be avoided: Barbituric acid derivatives: barbiturates (the study was conducted with fenofarbital) slightly increase metabolism of metoprolol, due to the induction of enzymes. 5 times, while two patients had side effects characteristic of metoprolol. This interaction was confirmed during the study on 8 volunteers. The interaction is likely due to the inhibition by propafenone, like quinidine, of the metabolism of metoprolol through the cytochrome P4502D6 system. Taking into account the fact that propafenone has the properties of β-blocker, the joint appointment of metoprolol and propafenone does not seem appropriate. Verapamil: a combination of β-blockers (atenolol, propranolol and pindolol) and verapamil can cause bradycardia and lead to a decrease in blood pressure.Verapamil and β-blockers have a complementary inhibitory effect on atrio-ventricular conductivity and sinus node function. Combining Betaloc with the following drugs may require dose adjustment: Class I antiarrhythmic drugs: Class I antiarrhythmics and β-blockers can result in the summation of negative inotropics and IOTs. which can lead to serious hemodynamic side effects in patients with impaired left ventricular function. Similar combinations should also be avoided in patients with sick sinus syndrome and AV conduction disorders. The interaction is described on the example of disopyramide. Amiodarone: The combined use of amiodarone and metoprolol can lead to severe sinus bradycardia. Taking into account the extremely long half-life of amiodarone (50 days), possible interactions should be considered after a long time after the cancellation of amiodarone. Diltiazem: Diltiazem and β-blockers mutually enhance the inhibitory effect on AV conduction and the function of the sinus node. When metoprolol was combined with diltiazem, there were cases of severe bradycardia. Non-steroidal anti-inflammatory drugs (NSAIDs): NSAIDs weaken the antihypertensive effect of β-blockers. This interaction is most documented for indomethacin. The observed interaction for sulindac was not observed. In the studies with diclofenac, the described reaction was not observed. Diphenhydramine: Diphenhydramine reduces the clearance of metoprolol to α-hydroxymetoprolol 2.5 times. At the same time, there is an increase in the action of metoprolol. Epinephrine (adrenaline): 10 cases of severe arterial hypertension and bradycardia have been reported in patients taking non-selective β-adrenergic blockers (including pindolol and propranolol) and treated with epinephrine (adrenaline). Interaction is also noted in the group of healthy volunteers. It is assumed that such reactions can be observed with the use of epinephrine in conjunction with local anesthetics in case of accidental contact with the vascular bed. It is assumed that this risk is much lower when using cardioselective β-blockers. Phenylpropanolamine: Phenylpropanolamine (norephedrine) in a single dose of 50 mg can cause an increase in diastolic blood pressure to pathological values in healthy volunteers. Propranolol mainly prevents an increase in blood pressure caused by phenylpropanolamine.However, β-adrenergic blockers can cause reactions of paradoxical arterial hypertension in patients receiving high doses of phenylpropanolamine. Several cases of hypertensive crisis have been reported in patients receiving phenylpropanolamine. Quinidine: Quinidine inhibits the metabolism of metoprolol in a special group of patients with rapid hydroxylation (approximately 90% of the population in Sweden), causing a significant increase in the plasma concentration of metoprolol and an increase in β-blockade. It is believed that this interaction is also characteristic of other β-blockers in the metabolism of which cytochrome P4502D6 is involved. Clonidine: Hypertensive reactions with abrupt withdrawal of clonidine may be enhanced by co-administration of β-blockers. When combined, in case of clonidine withdrawal, discontinuation of β-adrenergic blockers should be started a few days before clonidine is withdrawn. Rifampicin: Rifampicin may increase metabolism of metoprolol, reducing the plasma concentration of metoprolol. , selective serotonin inhibitors, such as paroxetine, fluoxetine and sertraline. Patients simultaneously taking metoprolol and other β-adrenergic blockers (eye drops) or monoamine oxidase inhibitors (MAO) should be closely monitored. While taking β-adrenergic blockers, inhalation anesthetics enhance the cardiodepressive effect. While taking β-blockers, patients receiving oral hypoglycemic agents may need to adjust the dose of the latter. Cardiac glycosides when used together with β-blockers may increase the time of atrioventricular conductivity and cause bradycardia.
special instructions
Patients taking β-blockers, should not be administered intravenous blockers of "slow" calcium channels such as verapamil. Patients suffering from obstructive pulmonary disease are not recommended to prescribe β-blockers. In case of poor tolerability of other antihypertensive drugs or their ineffectiveness, you can prescribe metoprolol, because it is a selective drug.It is necessary to prescribe the minimum effective dose, if necessary, β2-adrenomimetic may be prescribed. When using β1-adrenergic blockers, the risk of their influence on carbohydrate metabolism or the possibility of masking the symptoms of hypoglycemia is much less than when using non-selective β-adrenergic blockers. In patients with chronic heart failure in the decompensation stage it is necessary to achieve the stage of compensation both before and during drug treatment. Patients suffering from Prinzmetal angina are not recommended to be prescribed nonselective β-adrenergic blockers. It is very rare in patients with impaired AV conduction to worsen (a possible outcome is AV blockade). If bradycardia has developed during treatment, the dose of Betaloc should be reduced or the drug should be gradually discontinued. Metoprolol may worsen the symptoms of disturbed peripheral circulation mainly due to a decrease in blood pressure. Caution should be exercised in the appointment of the drug to patients suffering from severe renal failure, with metabolic acidosis, co-administration with cardiac glycosides. Patients suffering from pheochromocytoma, along with the drug Betaloc should appoint an alpha-blocker. Patients with liver cirrhosis increases the bioavailability of metoprolol. In the case of surgery, the anesthesiologist should be informed that the patient is taking a β-blocker. Avoid abrupt withdrawal of the drug. If you need to cancel the drug, the abolition should be carried out gradually. In most patients, the drug can be canceled for 14 days. The dose of the drug is reduced gradually, in several doses, until the final dose of 25 mg is reached once a day. Patients with coronary heart disease should be under the close supervision of a physician during drug withdrawal. Patients taking β-blockers, anaphylactic shock proceeds in a more severe form. Effect on the ability to drive vehicles and control mechanisms With the use of the drug may be episodes of dizziness or general weakness, and therefore it is necessary to refrain from driving vehicles and classes of potentially dangerous activities, requiring increased concentration and speed of psychomotor reactions.